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Changes in the chemical makeup of cells can indicate the onset and progression of disorders such as neurodegenerative diseases, making it important to examine such changes in detail while focusing on the smallest possible areas. In the past, ambient sampling and ionization methods using electrospray ionization (ESI) for mass spectrometry imaging (MSI) have been developed.
ESI-based MSI uses a small probe to deliver solvent (a liquid that dissolves and releases chemical components) to a cell, detaching molecules that become charged and are then separated and counted in a mass spectrometer. Because mammalian cells can be as small as 10 micrometers, this imaging technique must be able to produce pixel sizes smaller than that.
"One issue with mass spectrometry imaging is that, as we focus on smaller and smaller regions within the cell, we require increasingly high sensitivity and stability," says lead author Takao Yasuda.
To address this issue, the researchers looked at ways to improve the performance of an ESI-based MSI system named tapping-mode scanning probe ESI (t-SPESI), which was originally invented by corresponding author Yoichi Otsuka. In the t-SPESI process, an extremely fine fused silica probe "taps" the cell repeatedly, alternately delivering a solvent and extracting components for analysis. This tapping motion enables the use of an extremely small amount of solvent to examine smaller areas but requires high sensitivity and good stability.
"Two factors currently limit the performance of this technique," senior author Otsuka says. "These are the long pathway between the probe and the mass spectrometer, and the tendency for cell components to adhere to the probe surface over time."
On this basis, the research team achieved higher sensitivity by miniaturizing the complex analytical apparatus, reducing device mass by 45% and ion pathway length by 56%. Shortening the tube more than doubled the signal intensity. To ensure long-term stability by reducing the adhesion of sample to the probe, the silica probe surface was coated with a fluorine-containing chemical, similar to a nonstick coating on a kitchen implement.
As a test of this new system, mouse brain tissue samples were analyzed, and the team successfully visualized lipid distributions, including lipid classes previously implicated in Alzheimer's and Parkinson's disease, with a pixel size of 5 micrometers, corresponding to fine tissue structures, and with good stability.
The team expects that examining cells within tissues using this technology will provide new insights for disease research and treatment. With further optimization, such as of probe size, even better performance could be achieved, helping future studies uncover the mechanisms behind many disorders and advancing understanding of them.
Publication details
Takao Yasuda et al, Development of a Tapping-Mode Scanning Probe Electrospray Ionization Platform for High-Sensitivity and Long-Term Stability in Single-Cell Mass Spectrometry Imaging of Tissue, Analytical Chemistry (2026). DOI: 10.1021/acs.analchem.6c02386
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Citation: New probe could help trace Alzheimer's-linked lipids one cell at a time (2026, July 8) retrieved 13 July 2026 from https://phys.org/news/2026-07-probe-alzheimer-linked-lipids-cell.html
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